The natural history of classic galactosemia: lessons from the GalNet registry.

BACKGROUND Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. METHODS Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. RESULTS Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. CONCLUSION This study describes the natural history of classic galactosemia based on the hitherto largest data set

Registro Nacional de la nutrición parenteral domiciliaria del año 2002 The year 2002 national register on home-based parenteral nutrition

Objetivo: Comunicar los resultados del registro sobre Nutrición Parenteral Domiciliaria (NPD) del grupo de Trabajo NADYA-SENPE, correspondientes al año 2002. Material y métodos: Recopilación de los datos del registro introducidos por las Unidades responsables de la atención de los pacientes con NPD. Se trata de un registro "on-line" disponible para los usuarios autorizados en la página web del grupo (www.nadya-senpe.com). Se recogen datos epidemiológicos, diagnóstico, vía de acceso, complicaciones, ingresos hospitalarios, grado de incapacidad y evolución a 31 de diciembre de 2002. Resultados: Se recogieron datos de 74 pacientes (56,8% mujeres y 43,2% hombres) pertenecientes a 18 centros hospitalarios. La edad media de los pacientes adultos fue de 49,4 ± 15,5 años; mientras que fue de 2,3 ± 1,1 años para los menores de 14 años (n = 3 pacientes). Las enfermedades que motivaron el uso de NPD fueron la isquemia mesentérica (29,7%), seguida de enfermedad neoplásica (16,2%), enteritis rádica (12,2%), alteraciones de la motilidad (8,1%) y enfermedad de Crohn (5,4%). Los catéteres tunelizados fueron empleados en el 52,7% de los casos, frente al 36,5% de reservorios subcutáneos. La duración media del tratamiento ha sido de 8,7 ± 4,4 meses; el 68,9% de los pacientes habían permanecido con NPD por un periodo superior a los 6 meses, y un 41,9% más de un año. El seguimiento del paciente fue mayoritariamente realizado desde el hospital de referencia (87,8%), y el 12,5% restante por el equipo de atención domiciliaria. En ningún caso el paciente fue seguido por el equipo de atención primaria o por otros especialistas distintos de los que indicaron el soporte nutricional. Se presentaron complicaciones relacionadas con el tratamiento nutritivo en 94 ocasiones. De las complicaciones, las que se presentaron con más frecuencia fueron las infecciosas. Estas complicaciones significaron 1,84 hospitalizaciones por paciente. El número medio de consultas fue de 12,9 consultas por paciente (10,2 rutinarias y 2,7 urgentes). Al finalizar el año, observamos que seguían en activo en el programa el 74,3% de los pacientes; mientras que el 23,6% restante la NPD había sido suspendida. Las principales causas de retirada fueron por éxitus (52,9%) y por pasar a depender de dieta oral (23,5%) o a nutrición enteral (11,8%). En cuanto al grado de incapacidad, el 16,1% estaban confinados en silla o cama y el 17,6% no presentaba ningún grado de incapacidad o sólo una leve incapacidad social Conclusiones: Observamos un mantenimiento en la tasa de prevalencia de NPD en España (1,8 pacientes/millón de habitantes). La causa principal de empleo fue el síndrome de intestino corto secundario a patología vascular, seguido del cáncer. Las complicaciones asociadas al tratamiento nutricional fueron frecuentes, especial-mente las de causa infecciosa.Aim: To report on the results of the Registry on Home-based Parenteral Nutrition (HPN) of the NADYASENPE working group, corresponding to the year 2002. Materials and method: Compilation of the registry data loaded by the Units in charge of HPN patients care. It consists of an on-line registry available to the registered users of the group's web page (www.nadya-senpe.com). Epidemiological, diagnostic, access route, complications, hospital admissions, degree of disability, and course until December 31st of 2002. Results: Data from 74 patients were gathered (56.8% women and 43.2% men), from 18 hospital centers. Mean age of adult patients was 49.4 ± 15.5 years and 2.3 ± 1.1 years for patients younger than 14 years (n = 3 patients). Diseases that prompted the use of HPN were mesenteric ischemia (29.7%), followed by neoplasms (16.2%), radiation enteritis (12.2%), motility impairments (8.1%), and Crohn' s disease (5.4%). Tunneled catheters were used in 52.7% of cases, as compared to 36.5% of subcutaneous reservoirs. Mean treatment duration was 8.7 ± 4.4 months; 68.9% of patients remained on HPN for a duration longer than 6 months, and in 41.9% longer than one year. Patients' follow-up was mainly done from the reference hospital (87.8%), and the remaining patients (12.5%) by the home care team. In no case patients were followed by the primary care team or other specialists than the ones that prescribed nutritional support. In 94 cases there were complications related to nutritional therapy. The more frequent complications presented were infectious. These complications represented 1.84 admissions per patient. The mean number of visits was 12.9 per patient (10.2 routinary visits and 2.7 emergency visits). At the end of the year, we observed that 74.3% patients stayed in the program, whereas in the remaining 23.6% HPN had been discontinued. The main causes for discontinuation were death (52.9%), and switch to oral diet (23.5%) or enteral nutrition (11.8%). With regards to disability degree, 16.1% were confined to a wheelchair or bed, and 17.6% had no disability at all or only a mild social disability. Conclusions: We observed a sustained HPN prevalence rate in Spain (1.8 patient pmp). The main cause for its use was short bowel syndrome secondary to vascular disease, followed by cancer. Complications associated to nutritional therapy were common, especially of infectious origin

Fertility in adult women with classic galactosemia and primary ovarian insufficiency

To study pregnancy chance in adult women with classic galactosemia and primary ovarian insufficiency. Despite dietary treatment, >90% of women with classic galactosemia develop primary ovarian insufficiency, resulting in impaired fertility. For many years, chance of spontaneous conception has not been considered, leading to counseling for infertility. But an increasing number of reports on pregnancies in this group questions whether current counseling approaches are correct.status: publishe

The natural history of classic galactosemia : Lessons from the GalNet registry

Background: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. Methods: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. Results: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. Conclusion: This study describes the natural history of classic galactosemia based on the hitherto largest data set

The natural history of classic galactosemia: lessons from the GalNet registry

BACKGROUND: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. METHODS: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. RESULTS: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. CONCLUSION: This study describes the natural history of classic galactosemia based on the hitherto largest data set.status: publishe